Over the past 15 years the Division of Clinical Sciences of the Fred Hutchinson Cancer Research Center has been involved in a continuing program of marrow transplantation for the treatment of patients with otherwise fatal malignant and nonmalignant hematologic diseases. A number of patients have become long- term survivors with well functioning grafts and neither recurrence of their original disease nor occurrence of graft-versus-host disease. Many patients, however, have died because of graft failure, recurrent disease, or complications related to graft- versus-host disease. Further improvement of clinical marrow grafting results hinge upon this progress and better understanding in at least 5 major areas of study: 1) Methods of diagnosing, preventing and treating acute and chronic graft-versus-host disease, 2) reconstitution of immunological reactivity in marrow graft recipients, 3) lymphocyte marrow-cell interactions, 4) resistance to marrow grafts, and 5) immune mechanisms of graft- versus-host disease. It is the objective of this proposal to carry out immunological investigations in those 5 areas of study.